Sulfonamides In The Treatment Of Glaucoma

Glaucoma is a chronic, degenerative eye disease, characterized by high IOP, which causes irreversible damage to the optic nerve head, and, as a result, the progressive loss of visual function and eventually blindness (Bartlett and Jaanus 1989; Maren 1992, 1995). Elevated IOP (ocular hypertension) is generally indicative of an early stage of the disease (Bartlett and Jaanus 1989; Soltau and Zimmerman 2002; Hoyng and Kitazawa 2002). CAIs represent the most physiological treatment of glaucoma, because by inhibiting the ciliary process enzyme (the sulfonamide susceptible isozymes CA II and CA IV), a reduced rate of bicarbonate and aqueous humor secretion is achieved, which leads to a 25 to 30% decrease in IOP (Maren 1967, 1992, 1995). Acetazolamide 8.1, methazolamide 8.2, ethoxzolamide 8.3 or dichlo-rophenamide 8.4 were and are still extensively used as systemic drugs in the therapy of this disease (Maren 1967; Supuran and Scozzafava 2000, 2001, 2002; Supuran et al. 2003), as they all act as very efficient inhibitors of several CA isozymes (Table 8.1), principally of CA II and CA IV, the two isozymes involved in aqueous humor secretion (Maren 1967, 1992, 1995).

The best-studied drug is acetazolamide, which has been frequently administered for years because of its efficient reduction of IOP, very reduced toxicity and ideal pharmacokinetic properties (Wistrand and Lindqvist 1991). In long-term therapy, acetazolamide 8.1 is administered in doses of 250 mg every 6 h, whereas the more liposoluble, structurally related methazolamide 8.2 in doses of 25 to 100 mg thrice daily; an equal dosage of dichlorophenamide 8.4 is also useful in reducing ocular hypertension (Bartlett and Jaanus 1989). But as CAs are ubiquitous enzymes in vertebrates, administration of these systemic sulfonamides with such a high affinity

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